Our investigations of combined immunodeficiency (CID) in young horses has demonstrated that this is a fatal genetic defect in foals inherited as an autosomal recessive trait. Studies of B- and T-lymphocyte responses in vitro and in vivo indicate this defect in foals is very similar to CID in children. Our objectives are: 1) To evaluate methods of therapy in CID foals which may be useful for treatment of children with similar defects. We will try to reconsitute B- and T-cell function with fetal liver transplants and T-cell function with fetal thymus transplants. Another objective 2) Is to investigate the dunctional basis of CID in foals through in vivo and in vitro experiments testing the functional capacity of CID bone marrow cells and epithelial cells of the hypoplastic thymuses. The third objective 3) Is to define the biochemical defect and/or its expression in the lymphoid system and relate these findings to the absence of antibody and cell-mediated immunity. The final objective 4) Is to employ CID foals for basic immunological investigations concerning the synthesis and metabolism of Clq, and the development of the secretory immune system.